Publications - Working papers
Please find below working papers of our group. Currently, we list 58 working papers.
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Genome-Wide Analysis of Single Nucleotide Polymorphisms in Evolutionary Conserved DNA
Claudia Fried, Peter F. Stadler, Peter Ahnert
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Abstract
Variation databases promise to enable the assessment of recent selection pressure on genomic sequence elements. Evidence of recent selection would suggest recent functional relevance of elements potentially important for understanding the organization of the human genome and resulting complex phenotypes and diseases. In contrast, comparative sequence analysis can be employed to focus on those regions that have have been under long-term stabilizing selection. Previously observed biases in variation databases appear to have been reduced to the point that their data can now be used to for investigate the relationships of long-term sequence preservation and recent selective pressures. In a genome-wide study, we identified phylogenetic footprints (PFs) in the vicinity of human genes. In agreement with the distribution of known regulatory sites, the density of these PFs was highest within two thousand base pairs upstream and downstream of genes. Stabilizing selection acting on these PFs was most strongly indicated by significantly reduced single nucleotide polymorphism (SNP) density. Weak correlation between SNP densities of PFs and coding sequences suggests that gene regulation and function often evolve independently. Decreasing diversity in human genes with increasing time of conservation suggests that most old genes have not ceased to be functionally important today. On average, intergenic sequences are under the least selection pressure in the vicinity of genes and may serve as a preferred model for estimating neutral evolution. Intriguingly, we observed increased SNP densities in coding sequences and introns as compared to non-coding sequences of genes conserved only among primates. These genes appear to be mainly involved in the regulation of gene expression and raise the question about mechanisms for adaptive evolution and their role in primate development.
Keywords
Sequence Homology, Nucleic Acid, Evolution, Phylogeny, Single Nucleotide Polymorphism, Genome, Transcription Factors, Gene Expression Regulation